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Primary cilia

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https://www.readbyqxmd.com/read/27913685/novel-biomarkers-in-kidney-disease-roles-for-cilia-wnt-signalling-and-atmin-in-polycystic-kidney-disease
#1
REVIEW
Paraskevi Goggolidou, Patricia D Wilson
Biomarkers, the measurable indicators of biological conditions, are fast becoming a popular approach in providing information to track disease processes that could lead to novel therapeutic interventions for chronic conditions. Inherited, chronic kidney disease affects millions of people worldwide and although pharmacological treatments exist for some conditions, there are still patients whose only option is kidney dialysis and kidney transplantation. In the past 10 years, certain chronic kidney diseases have been reclassified as ciliopathies...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911709/shuttling-and-sorting-lipid-modified-cargo-into-the-cilia
#2
REVIEW
Louise A Stephen, Shehab Ismail
Primary cilia are hair-like microtubule-based organelles that can be found on almost all human cell types. Although the cilium is not separated from the cell by membranes, their content is different from that of the cell body and their membrane composition is distinct from that of the plasma membrane. Here, we will introduce a molecular machinery that shuttles and sorts lipid-modified proteins to the cilium, thus contributing in maintaining its distinct composition. The mechanism involves the binding of the GDI-like solubilising factors, uncoordinated (UNC)119a, UNC119b and PDE6D, to the lipid-modified ciliary cargo and the specific release of the cargo in the cilia by the ciliary small G-protein Arl3 in a GTP-dependent manner...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911708/regulation-of-primary-cilia-formation-by-the-ubiquitin-proteasome-system
#3
REVIEW
Robert F Shearer, Darren N Saunders
Primary cilia form at the surface of most vertebrate cell types, where they are essential signalling antennae for signal transduction pathways important for development and cancer, including Hedgehog. The importance of primary cilia in development is clearly demonstrated by numerous disorders (known as ciliopathies) associated with disrupted cilia formation (ciliogenesis). Recent advances describing functional regulators of the primary cilium highlight an emerging role for the ubiquitin-proteasome system (UPS) as a key regulator of ciliogenesis...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911704/primary-cilia-a-link-between-hormone-signalling-and-endocrine-related-cancers
#4
REVIEW
Samuel M O'Toole, J Paul Chapple
Primary cilia are sensory organelles that play a role as signalling hubs. Disruption of primary cilia structure and function is increasingly recognised in a range of cancers, with a growing body of evidence suggesting that ciliary disruption contributes to tumourigenesis. This review considers the role of primary cilia in the pathogenesis of endocrine-related cancers.
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27908937/the-centrosome-a-multitalented-renaissance-organelle
#5
REVIEW
Anastassiia Vertii, Heidi Hehnly, Stephen Doxsey
The centrosome acts as a microtubule-organizing center (MTOC) from the G1 to G2 phases of the cell cycle; it can mature into a spindle pole during mitosis and/or transition into a cilium by elongating microtubules (MTs) from the basal body on cell differentiation or cell cycle arrest. New studies hint that the centrosome functions in more than MT organization. For instance, it has recently been shown that a specific substructure of the centrosome-the mother centriole appendages-are required for the recycling of endosomes back to the plasma membrane...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27903126/potential-evolution-of-neurosurgical-treatment-paradigms-for-craniopharyngioma-based-on-genomic-and-transcriptomic-characteristics
#6
Leslie C Robinson, Sandro Santagata, Todd C Hankinson
The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27900292/hypoxia-inhibits-primary-cilia-formation-and-reduces-cell-mediated-contraction-in-stress-deprived-rat-tail-tendon-fascicles
#7
Michael Lavagnino, Anna N Oslapas, Keri L Gardner, Steven P Arnoczky
BACKGROUND: Hypoxia, which is associated with chronic tendinopathy, has recently been shown to decrease the mechanosensitivity of some cells. Therefore, the purpose of this study was to determine the effect of hypoxia on the formation of elongated primary cilia (a mechanosensing organelle of tendon cells) in vitro and to determine the effect of hypoxia on cell-mediated contraction of stress-deprived rat tail tendon fascicles (RTTfs). METHODS: Tendon cells isolated from RTTfs were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions for 24 hours...
April 2016: Muscles, Ligaments and Tendons Journal
https://www.readbyqxmd.com/read/27881449/primary-cilia-and-mammalian-hedgehog-signaling
#8
Fiona Bangs, Kathryn V Anderson
It has been a decade since it was discovered that primary cilia have an essential role in Hedgehog (Hh) signaling in mammals. This discovery came from screens in the mouse that identified a set of genes that are required for both normal Hh signaling and for the formation of primary cilia. Since then, dozens of mouse mutations have been identified that disrupt cilia in a variety of ways and have complex effects on Hedgehog signaling. Here, we summarize the genetic and developmental studies used to deduce how Hedgehog signal transduction is linked to cilia and the complex effects that perturbation of cilia structure can have on Hh signaling...
November 23, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27875681/subdistal-appendages-stabilize-the-ups-and-downs-of-ciliary-life
#9
Domenico F Galati, Brian J Mitchell, Chad G Pearson
Centrioles acquire subdistal appendages (sDAPs) during primary cilium formation. In this issue of Developmental Cell, Mazo et al. (2016) demonstrate that sDAPs keep cilia submerged within deep membrane invaginations. When sDAPs and centrosome cohesion are disrupted, cilia surface to the plasma membrane, which may alter mechanical and chemical signal transduction.
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27872140/primary-cilia-are-increased-in-number-and-demonstrate-structural-abnormalities-in-human-cancer
#10
Binnaz Yasar, Kim Linton, Christian Slater, Richard Byers
AIMS: Primary cilia play an important role in the regulation of cell signalling pathways and are thought to have a role in cancer but have seldom been studied in human cancer samples. METHODS: Primary cilia were visualised by dual immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin in a range of human cancers (including carcinomas of stomach, pancreas, prostate, lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in matched normal tissue (stomach, pancreas, lung, large and small intestines, breast and reactive lymph nodes) samples using a tissue microarray; their frequency, association with proliferation, was measured by Ki-67 staining and their structure was analysed...
November 21, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27866888/comparative-analysis-of-ciliary-membranes-and-ectosomes
#11
Huan Long, Fan Zhang, Nannan Xu, Gai Liu, Dennis R Diener, Joel L Rosenbaum, Kaiyao Huang
Primary and motile cilia/flagella function as cellular antennae, receiving signals from the environment and subsequently activating signaling pathways that are critical for cellular homeostasis and differentiation [1-3]. Recent work with the green alga Chlamydomonas and the nematode C. elegans demonstrated that ectosomes can be released from the cilium and can mediate the intercellular communication [4-9]. To better understand the function of flagellar ectosomes, we have compared their protein composition to that of the flagellar membrane from which they are derived...
November 10, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27864314/cilia-and-mucociliary-clearance
#12
Ximena M Bustamante-Marin, Lawrence E Ostrowski
Mucociliary clearance (MCC) is the primary innate defense mechanism of the lung. The functional components are the protective mucous layer, the airway surface liquid layer, and the cilia on the surface of ciliated cells. The cilia are specialized organelles that beat in metachronal waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways. In health this clearance mechanism is effective, but in patients with primary cilia dyskinesia (PCD) the cilia are abnormal, resulting in deficient MCC and chronic lung disease...
November 18, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27861880/the-multifaceted-roles-of-primary-cilia-in-the-regulation-of-stem-cell-properties-and-functions
#13
REVIEW
Rui Lyu, Jun Zhou
Stem cells are a unique class of cells that are capable of self-renewal and differentiation into multiple lineages. An increasing number of studies have suggested that both embryonic and adult stem cells possess primary cilia, antenna-like structures protruding from cell surfaces that are critical for sensing and transducing environmental cues. The primary cilium appears to regulate stem cells in multiple aspects, such as lineage specification and stemness maintenance. Understanding the role of primary cilia in the control of stem cell behavior could lead to the identification of new targets for regenerative therapies...
November 11, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27853007/bardet-biedl-syndrome-genetics-molecular-pathophysiology-and-disease-management
#14
REVIEW
Sathya Priya, Sheela Nampoothiri, Parveen Sen, S Sripriya
Primary cilia play a key role in sensory perception and various signaling pathways. Any defect in them leads to group of disorders called ciliopathies, and Bardet-Biedl syndrome (BBS, OMIM 209900) is one among them. The disorder is clinically and genetically heterogeneous, with various primary and secondary clinical manifestations, and shows autosomal recessive inheritance and highly prevalent in inbred/consanguineous populations. The disease mapped to at least twenty different genes (BBS1-BBS20), follow oligogenic inheritance pattern...
September 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27829053/no-evidence-for-ionotropic-pheromone-transduction-in-the-hawkmoth-manduca-sexta
#15
Andreas Nolte, Petra Gawalek, Sarah Koerte, HongYing Wei, Robin Schumann, Achim Werckenthin, Jürgen Krieger, Monika Stengl
Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27825103/primary-cilia-are-sensors-of-electrical-field-stimulation-to-induce-osteogenesis-of-human-adipose-derived-stem-cells
#16
Shaobo Cai, Josephine C Bodle, Pattie S Mathieu, Alison Amos, Mehdi Hamouda, Susan Bernacki, Greg McCarty, Elizabeth G Loboa
In this study, we report for the first time that the primary cilium acts as a crucial sensor for electrical field stimulation (EFS)-enhanced osteogenic response in osteoprogenitor cells. In addition, primary cilia seem to functionally modulate effects of EFS-induced cellular calcium oscillations. Primary cilia are organelles that have recently been implicated to play a crucial sensor role for many mechanical and chemical stimuli on stem cells. Here, we investigate the role of primary cilia in EFS-enhanced osteogenic response of human adipose-derived stem cells (hASCs) by knocking down 2 primary cilia structural proteins, polycystin-1 and intraflagellar protein-88...
October 19, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27818179/spatial-control-of-primary-ciliogenesis-by-subdistal-appendages-alters-sensation-associated-properties-of-cilia
#17
Gregory Mazo, Nadine Soplop, Won-Jing Wang, Kunihiro Uryu, Meng-Fu Bryan Tsou
Vertebrate cells can initiate ciliogenesis from centrioles at the cell center, near the Golgi, forming primary cilia confined or submerged in a deep narrow pit created by membrane invagination. How or why cells maintain submerged cilia is unclear. Here, by characterizing centriole subdistal appendages (sDAP) in cells exclusively growing submerged cilia, we found that a group of sDAP components localize to the centriole proximal end through the cohesion factor C-Nap1 and that sDAP function redundantly with C-Nap1 for submerged cilia maintenance...
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27816963/defective-ciliogenesis-in-thyroid-h%C3%A3-rthle-cell-tumors-is-associated-with-increased-autophagy
#18
Junguee Lee, Shinae Yi, Yea Eun Kang, Joon Young Chang, Jung Tae Kim, Hae Joung Sul, Jong Ok Kim, Jin Man Kim, Joon Kim, Anna Maria Porcelli, Koon Soon Kim, Minho Shong
Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27812213/hif-stabilization-weakens-primary-cilia
#19
Andrew Resnick
Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Defective cilia and ciliary-associated proteins have been shown to result in cystic diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States...
2016: PloS One
https://www.readbyqxmd.com/read/27802276/craniofacial-ciliopathies-reveal-specific-requirements-for-gli-proteins-during-development-of-the-facial-midline
#20
Ching-Fang Chang, Ya-Ting Chang, Grethel Millington, Samantha A Brugmann
Ciliopathies represent a broad class of disorders that affect multiple organ systems. The craniofacial complex is among those most severely affected when primary cilia are not functional. We previously reported that loss of primary cilia on cranial neural crest cells, via a conditional knockout of the intraflagellar transport protein KIF3a, resulted in midfacial widening due to a gain of Hedgehog (HH) activity. Here, we examine the molecular mechanism of how a loss of primary cilia can produce facial phenotypes associated with a gain of HH function...
November 2016: PLoS Genetics
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